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Published on: February 2, 2024
Pancreatic cancer and oligonucleotide therapy: Exploring novel therapeutic options and targeting chemoresistance
Apostolis Papaefthymiou1, Aris Doukatas2, Michail Galanopoulos3
1Department of Gastroenterology, University Hospital of Larissa, Larissa, 41110, Thessaly, Greece.
Abstract:
Pancreatic cancer (PC) represents a malignancy with increased mortality rate, as less than 10% of patients survive for 5 years after diagnosis. Current evolution in basic sciences has revealed promising results by decrypting genetic loci vulnerable to mutations, as potential targets of novel treatment choices. In this regard, the "Oligonucleotide therapeutics", based on synthetic nucleotides, modify the function and expression of their targets. Antisense oligonucleotides (ASOs), small interfering RNA (siRNA), microRNAs (miRNAs), aptamers, CpG oligodeoxynucleotides and decoys comprise the main representatives of this emerging technology, by regulating oncogenes' expression, restoring DNA repairment mechanisms, sensitizing cancer cells in chemotherapy, and inhibiting PC progress. A plethora of genetic treatment molecules and respective targets have been described and are currently studied, thus providing a broad range of probable pharmaceutical options. This narrative review illuminates the main parameters of genetic treatment molecules for PC and underlines their deficiencies, to clarify the upcoming future and trigger further investigation in PC management.
Insights
Oligonucleotide therapeutics offer new hope for pancreatic cancer (PC) treatment by targeting genetic mutations. This review explores these novel therapies, including antisense oligonucleotides (ASOs) and small interfering RNA (siRNA), for improved PC management.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pancreatic cancer (PC) has a high mortality rate with less than 10% 5-year survival.
- Advances in basic science identify genetic mutations as potential therapeutic targets for PC.
Purpose of the Study:
- To review oligonucleotide therapeutics for pancreatic cancer.
- To discuss the mechanisms, targets, and deficiencies of these emerging treatments.
Main Methods:
- This narrative review analyzes current research on oligonucleotide therapeutics for PC.
- Key therapeutic molecules such as antisense oligonucleotides (ASOs), small interfering RNA (siRNA), microRNAs (miRNAs), aptamers, CpG oligodeoxynucleotides, and decoys are discussed.
Main Results:
- Oligonucleotide therapeutics can regulate oncogene expression, restore DNA repair, sensitize cells to chemotherapy, and inhibit PC progression.
- Various genetic targets and therapeutic molecules are under investigation, offering diverse pharmaceutical options.
Conclusions:
- Oligonucleotide therapeutics represent a promising avenue for pancreatic cancer treatment.
- Further research is needed to address the deficiencies of these genetic molecules for effective PC management.
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